Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains—responsible use, surveillance, and infection prevention and control—and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions

Suppressing quantum errors by scaling a surface code logical qubit

Practical quantum computing will require error rates that are well below what is achievable with physical qubits. Quantum error correction offers a path to algorithmically-relevant error rates by encoding logical qubits within many physical qubits, where increasing the number of physical qubits enhances protection against physical errors. However, introducing more qubits also increases the number of error sources, so the density of errors must be sufficiently low in order for logical performance to improve with increasing code size. Here, we report the measurement of logical qubit performance scaling across multiple code sizes, and demonstrate that our system of superconducting qubits has sufficient performance to overcome the additional errors from increasing qubit number. We find our distance-5 surface code logical qubit modestly outperforms an ensemble of distance-3 logical qubits on average, both in terms of logical error probability over 25 cycles and logical error per cycle ($2.914\%\pm 0.016\%$ compared to $3.028\%\pm 0.023\%$). To investigate damaging, low-probability error sources, we run a distance-25 repetition code and observe a $1.7\times10^{-6}$ logical error per round floor set by a single high-energy event ($1.6\times10^{-7}$ when excluding this event). We are able to accurately model our experiment, and from this model we can extract error budgets that highlight the biggest challenges for future systems. These results mark the first experimental demonstration where quantum error correction begins to improve performance with increasing qubit number, illuminating the path to reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references, Fig. S12, Table I

Measurement-induced entanglement and teleportation on a noisy quantum processor

Measurement has a special role in quantum theory: by collapsing the wavefunction it can enable phenomena such as teleportation and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time that go beyond established paradigms for characterizing phases, either in or out of equilibrium. On present-day NISQ processors, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping, to avoid mid-circuit measurement and access different manifestations of the underlying phases -- from entanglement scaling to measurement-induced teleportation -- in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

A screen for E3 ubiquitination ligases that genetically interact with the adaptor protein Cindr during Drosophila eye patterning.

Ubiquitination is a crucial post-translational modification that can target proteins for degradation. The E3 ubiquitin ligases are responsible for recognizing substrate proteins for ubiquitination, hence providing specificity to the process of protein degradation. Here, we describe a genetic modifier screen that identified E3 ligases that modified the rough-eye phenotype generated by expression of cindrRNAi transgenes during Drosophila eye development. In total, we identified 36 E3 ligases, as well as 4 Cullins, that modified the mild cindrRNA mis-patterning phenotype. This indicates possible roles for these E3s/Cullins in processes that require Cindr function, including cytoskeletal regulation, cell adhesion, cell signaling and cell survival. Three E3 ligases identified in our screen had previously been linked to regulating JNK signaling

Modification of the rough-eye phenotype by alleles of E3 ligases linked to JNK signaling.

<p>(A) A correctly patterned heterozygous <i>GMR-GAL4/+</i> eye. (B) Mild mis-patterning manifested as mildly disordered facets that were not arranged in straight rows in the <i>GMR>cindr</i>^<i>RNAi</i> eye. Mis-patterning was suppressed by (C) ectopic <i>nopo</i> (<i>nopo</i>^<i>G5845</i>) but (D) on its own, <i>nopo</i> expression did not disrupt the eye. (E) <i>park</i>^{<i>c00062</i>} enhanced <i>cindr</i>^<i>RNAi</i> mis-patterning whilst (F) <i>park</i>^<i>1</i> and (G) <i>park</i>^Δ21 suppressed <i>cindr</i>^<i>RNAi</i> mis-patterning. (H) <i>Traf6</i>^<i>EP325</i> and (I) <i>Traf6</i>^{<i>EP1516</i>} also modestly suppressed the <i>cindr</i>^<i>RNAi</i> rough eye. (J) <i>Traf6</i>^<i>EP325</i> and (K) <i>Traf6</i>^{<i>EP1516</i>} did not disrupt the eye when crossed to <i>GMR-GAL4</i>.</p

List of E3 ligase and Cullin proteins tested in screen.

<p>List of E3 ligase and Cullin proteins tested in screen.</p

Patterning of the pupal retinal was modified by interactions between <i>park</i>, <i>nopo</i> and <i>Traf6</i> and <i>cindr</i>.

<p>(A) A single ommatidium in a wild-type eye dissected at 40 h APF, with constituent cell types indicated. Photoreceptors are positioned beneath the surface of the tissue and not clearly observed in this image of the apical eye surface. (B) Small region of a correctly patterned control pupal retina and (C) retina expressing <i>cindr</i>^<i>RNAi</i> together with <i>lacZ</i> or (D) only <i>cindr</i>^<i>RNAi</i>. Expression of (E) <i>nopo</i>^<i>G5845</i>, (F) <i>nopo</i>^<i>G5845</i> and <i>cindr</i>^<i>RNAi</i>. (G) Expression of <i>cindr</i>^<i>RNAi</i> in a <i>nopo</i>^{<i>excl42</i>} heterozygote and (H) <i>nopo</i>^<i>Z1447</i> heterozygote. Expression of (I) <i>park</i>, (J) <i>park</i> and <i>cindr</i>^<i>RNAi</i>. (K) Expression of <i>cindr</i>^<i>RNAi</i> in a <i>park</i>^<i>1</i> heterozygote and (L) <i>park</i>^Δ21, heterozygote. (M) Expression of <i>Traf6</i>^<i>S</i> and (N) <i>Traf6</i>^<i>S</i> and <i>cindr</i>^<i>RNAi</i>. Anti-ECad was used to visualize all adherens junctions of retinas. Fluorescence images have been transformed into greyscale and interommatidial cells pseudo-colored red in order to highlight the honeycomb lattice. Examples of patterning defects are indicated as follows: blue arrow = mis-orientation of ommatidial core; outlined in green = small primary pigment cells; yellow circle = tertiary position not defined; blue circle = bristle misplaced and star-like arrangement of cells around bristle; orange asterisks = two cells rather than one in a secondary pigment cell position; blue asterisks = cells grouped in multiple rows rather than single file.</p

The <i>cindr</i>^<i>RNAi</i> eye is modified by JNK activity.

<p>(A) Eye of a <i>GMR-GAL4</i> heterozygote and (B) <i>GMR>cindr</i>^<i>RNAi</i> adult. (C) <i>cindr</i>^<i>RNAi</i>–induced mis-patterning was mildly enhanced by ectopic <i>bsk</i> (D) but (D) on its own <i>bsk</i> expression did not disrupt the eye. Similarly (E) ectopic <i>slpr</i> enhanced the <i>cindr</i>^<i>RNAi</i> rough eye but (F) the <i>GMR>slpr</i> adult eye was correctly formed. (G) <i>puc</i>^<i>H246</i>, (H) <i>bsk</i>^<i>1</i> and (I) ectopic <i>puc</i> enhanced <i>cindr</i>^<i>RNAi</i>- mis-patterning, whilst (J) expression of only <i>puc</i> did not perturb patterning. Similarly (K) <i>Traf4</i>^{<i>EY0977</i>1} enhanced the <i>GMR>cindr</i>^<i>RNAi</i> rough eye whilst (L) <i>GMR>Traf4</i>^{<i>EY09771</i>} adults had correctly patterned eyes. (M) <i>Uev1a</i>^{<i>DG14805</i>} severely enhanced the <i>GMR>cindr</i>^<i>RNAi</i> rough eye.</p